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Hydrophosphination

Hydrophosphination is the insertion of a double bond into a phosphorus-hydrogen bond. Often the hydrophosphination makes phosphorus-carbon bonds by addition of P-H bonds to carbon-carbon multiple bonds, but the reaction is probably most useful in reactions of phosphine with formaldehyde, a form of hydroxymethylation.

Like other hydrofunctionalizations, the rate and regiochemistry of the insertion reaction is influenced by the catalyst. Catalysts take many forms, but most prevalent are bases and free-radical initiators. Most hydrophosphinations involve reactions of phosphine (PH3).

Hydroxyalkylation

Although most of this article concerns addition of P-H bonds to alkenes, an important variant is the hydrophosphination of formaldehyde. Tetrakis(hydroxymethyl)phosphonium chloride (THPC) is prepared as follows from phosphine:

PH<sub>3</sub> + 4 H<sub>2</sub>C=O + HCl → [P(CH<sub>2</sub>OH)<sub>4</sub>]Cl

It is a white water-soluble salt with applications as a precursor to fire-retardant materials and as a microbiocide in commercial and industrial water systems. The hydroxymethyl groups on THPC undergo replacement reactions when THPC is treated with α,β-unsaturated nitrile, acid, amide, and epoxides. For example, base induces condensation between THPC and acrylamide with displacement of the hydroxymethyl groups. (Z = CONH<sub>2</sub>)

[P(CH<sub>2</sub>OH)<sub>4</sub>]Cl + NaOH + 3 CH<sub>2</sub>=CHZ → P(CH<sub>2</sub>CH<sub>2</sub>Z)<sub>3</sub> + 4 CH<sub>2</sub>O + H<sub>2</sub>O + NaCl

Similar reactions occur when THPC is treated with acrylic acid; only one hydroxymethyl group is displaced, however.

THPC converts to tris(hydroxymethyl)phosphine upon treatment with aqueous sodium hydroxide:

[P(CH<sub>2</sub>OH)<sub>4</sub>]Cl + NaOH → P(CH<sub>2</sub>OH)<sub>3</sub> + H<sub>2</sub>O + H<sub>2</sub>C=O + NaCl

Acid-base routes

The usual application of hydrophosphination involves reactions of phosphine (PH<sub>3</sub>). Typically base-catalysis allows addition of Michael acceptors such as acrylonitrile to give tris(cyanoethyl)phosphine:

PH<sub>3</sub> + 3 CH<sub>2</sub>=CHZ → P(CH<sub>2</sub>CH<sub>2</sub>Z)<sub>3</sub> (Z = NO<sub>2</sub>, CN, C(O)NH<sub>2</sub>)

Acid catalysis is applicable to hydrophosphination with alkenes that form stable carbocations. These alkenes include isobutylene and many analogues:

PH<sub>3</sub> + R<sub>2</sub>C=CH<sub>2</sub> → R<sub>2</sub>(CH<sub>3</sub>)CPH<sub>2</sub> (R = Me, alkyl, etc)

Bases catalyze the addition of secondary phosphines to vinyldiphenylphosphine:

HPR<sub>2</sub> + CH<sub>2</sub>=CHPR'<sub>2</sub> → R<sub>2</sub>PCH<sub>2</sub>CH<sub>2</sub>PR'<sub>2</sub>

Free-radical methods

Many hydrophosphination reactions are initiated by free-radicals. AIBN and peroxides are typical initiators, as well as Ultraviolet irradiation. In this way, the commercially important tributylphosphine and trioctylphosphine are prepared in good yields from 1-butene and 1-octene, respectively.

The reactions proceed by abstraction of an H atom the phosphine precursor, producing the phosphino radical, a seven electron species. This radical then adds to the alkene, and subsequent H-atom transfer completes the cycle. Some highly efficient hydrophosphinations appear not to proceed via radicals, but alternative explanations are lacking.

Metal-catalyzed reactions

Metal-catalyzed hydrophosphinations are not widely used, although they have been extensively researched. Studies mainly focus on secondary and primary organophosphines (R<sub>2</sub>PH and RPH<sub>2</sub>, respectively). These substrates bind to metals, and the resulting adducts insert alkenes and alkynes into the P-H bonds via diverse mechanisms.

Early transition metal and lanthanide catalysts

Metal complexes of d<sup>0</sup> configurations are effective catalysts for hydrophosphinations of simple alkenes and alkynes. Intramolecular reactions are facile, e.g. starting with α,ω-pentenylphosphine. The primary phosphine undergoes a σ-bond metathesis with the bis(trimethylsilyl)methylene ligand forming the lanthanide-phosphido complex. Subsequently, the pendant terminal alkene or alkyne inserts into the Ln-P bond. Finally, protonolysis of the Ln-C bond with the starting primary phosphine releases the new phosphine and regenerates the catalyst. Given that the metal is electron-poor, the M-C bond is sufficiently enough to be protonolyzed by the substrate primary phosphine.

Most metal catalyzed hydrophosphinations proceed via metal phosphido intermediates. Some however proceed by metal-phosphinidene intermediates, i.e. species with M=PR double bonds. One such example is the Ti-catalyzed hydrophosphination of diphenylacetylene with phenylphosphine. This system involves a cationic catalyst precursor that is stabilized by the bulky 2,4,6-tri(isopropyl)phenyl- substituent on the phosphinidene and the close ionic association of methyltris(pentafluorophenyl)borate. This precursor undergoes exchange with phenylphosphine to give the titanium-phenylphosphinidene complex, which is the catalyst. The Ti=PPh species undergoes a [2+2] cycloaddition with diphenylacetylene to make the corresponding metallacyclobutene. The substrate, phenylphosphine, protonolyzes the Ti-C bond and after a proton shift regenerates the catalyst and releases the new phosphine.

Titanium-catalyzed 1,4-hydrophosphination of 1,3-dienes with diphenylphosphine has been demonstrated. It is a rare example of a d<sup>2</sup> catalyst. In the first step, the Ti(II) precursor inserted in the P-H bond of diphenylphosphine (Ph<sub>2</sub>PH).

Late transition metal catalysts

Late transition metal hydrophosphination catalysts, i.e. those reliant on the nickel-triad and neighboring elements, generally require alkenes and alkynes with electron withdrawing substituents. A strong base is required as a cocatalyst.

Some late metal hydrophosphination catalysts proceed via oxidative addition of a P-H bond. For example, a Pt(0) catalyst undergoes oxidative addition of a secondary phosphine to form the corresponding hydrido Pt(II) phosphido complex. These systems catalyze hydrophosphination of acrylonitrile, although this reaction can be achieved without metal catalysts. The key P-C bond-forming step occurs through an outer-sphere, Michael-type addition.

The usual mechanism for hydrophosphination for late metal catalysts involves insertion of the alkene into the metal-phosphorus bond. Insertion into the metal-hydrogen bond is also possible. The product phosphine is produced through reductive elimination of a P-C bond rather than a P-H bond in Glueck's system. The Ni(0) catalyst involves oxidation addition of a P-H bond to the metal, followed by insertion of the alkene into the M-H bond.

Main group catalysis

Calcium-catalysed intermolecular hydrophosphination is known, using a β-diketiminato complex.

Hydrophosphorylation and related reactions

Utilizing phosphorus(V) precursors hydrophosphorylation entails the insertion of alkenes and alkynes into the P-H bonds of secondary phosphine oxides:

R<sub>2</sub>P(O)H + CH<sub>2</sub>=CHR → R<sub>2</sub>P(O)CH<sub>2</sub>CH<sub>2</sub>R

The reaction can be effected both using metal catalysts or free-radical initiators.

Further reading

References